Greater than 98% of small molecule and nearly 100% of large molecule CNS drugs do not cross the BBB effectively. Intracerebroventricular or intraparenchymal administration can directly deliver therapeutics to the brain and/or cerebrospinal fluid; however, these methods are invasive, inconvenient, and impractical for the numbers of individuals requiring therapeutic interventions for treating CNS disorders. Intranasal administration of therapeutic compounds or polypeptides may, in some cases, increase the effectiveness of certain therapeutic compounds or polypeptides in bypassing the blood brain barrier (BBB) and delivering the compound or polypeptide directly to the CNS (e.g., brain and cerebrospinal fluid). Thus, intranasal administration of therapeutic compounds or polypeptides may allow increased prevention and/or treatment of certain diseases or conditions. Intranasal administration is a non-invasive and convenient means to rapidly target therapeutics of varying physical and chemical properties to the CNS.
The intranasal method of administration holds great promise as an alternative to more invasive routes; however, a number of factors limit the efficiency of intranasal administration to the CNS. Absorption of intranasally applied drugs into the capillary network in the nasal mucosa can decrease the amount of therapeutic available for direct transport into the CNS. Additional factors within the nasal cavity, including the presence of nasal mucociliary clearance mechanisms, metabolizing enzymes, efflux transporters and nasal congestion can also reduce the efficiency of delivery into the CNS. For example, therapeutic compounds or polypeptides may be absorbed into the blood and/or delivered to peripheral (non-target) tissues, thus reducing delivery of the compound to the CNS.